Evidence map›Paper›PMID 33835523›Full record

ArticleHistopathology2021

Performance of a HER2 testing algorithm specific for p53-abnormal endometrial cancer.

Lisa Vermij, Naveena Singh, Alicia Leon-Castillo, Nanda Horeweg, Jan Oosting, Joseph Carlson, Vincent Smit, Blake Gilks, Tjalling Bosse

Open access · hybridAbstract read
In one paragraph

Article in Histopathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 16 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Targeted and Shallow Whole-Genome Sequencing Identifies Therapeutic Opportunities in p53abn Endometrial Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  5. Article
  6. Article
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 4 countries.

Lisa VermijDepartment of Pathology, Leiden University Medical Center, Leiden, the Netherlands.ORCID https://orcid.org/0000-0003-4687-5550
Naveena SinghDepartment of Pathology, Barts Health NHS Trust, London, UK.ORCID https://orcid.org/0000-0003-1782-1967
Alicia Leon-CastilloDepartment of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Nanda HorewegDepartment of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Jan OostingDepartment of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Joseph CarlsonDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Vincent SmitDepartment of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Blake GilksDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.ORCID https://orcid.org/0000-0001-7889-8250
Tjalling BosseDepartment of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Leiden University Medical Center · NLBarts Health NHS Trust · GBKarolinska Institutet · SEUniversity of British Columbia · CA

Funding

Dutch Cancer Society Research Project 11629
6 · The paper itself

Abstract

aimsHuman epidermal growth factor receptor 2 (HER2) amplification in endometrial cancer (EC) is almost completely confined to the p53-abnormal (p53abn) molecular subtype and independent of histological subtype. HER2 testing should therefore be molecular subtype-directed. However, the most optimal approach for HER2 testing in EC has not been fully established. Therefore, we developed an EC-specific HER2 immunohistochemistry (IHC) scoring method and evaluated its reproducibility and performance to establish an optimal diagnostic HER2 testing algorithm for p53abn EC. METHODS AND

resultsHER2 IHC slides of 78 p53abn EC were scored by six gynaecopathologists according to predefined EC-specific IHC scoring criteria. Interobserver agreement was calculated using Fleiss' kappa and the first-order agreement coefficient (AC1). The consensus IHC score was compared with HER2 dual in-situ hybridisation (DISH) results. Sensitivity and specificity were calculated. A substantial interobserver agreement was found using three- or two-tiered scoring [κ = 0.675, 95% confidence interval (CI) = 0.633-0.717; AC1 = 0.723, 95% CI = 0.643-0.804 and κ = 0.771, 95% CI = 0.714-0.828; AC1 = 0.774, 95% CI = 0.684-0.865, respectively]. Sensitivity and specificity for the identification of HER2-positive EC was 100 and 97%, respectively, using a HER2 testing algorithm that recommends DISH in all cases with moderate membranous staining in >10% of the tumour (IHC+). Performing DISH on all IHC-2+ and -3+ cases yields a sensitivity and specificity of 100%.

conclusionsOur EC-specific HER2 IHC scoring method is reproducible. A screening strategy based on IHC scoring on all cases with subsequent DISH testing on IHC-2+/-3+ cases has perfect test accuracy for identifying HER2-positive EC.

Indexed as

AlgorithmsAgedAged, 80 and overBiomarkers, TumorEndometrial NeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleHumansImmunohistochemistryIn Situ HybridizationMiddle AgedSensitivity and SpecificityTumor Suppressor Protein p53Biomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesTP53 protein, humanTumor Suppressor Protein p53endometrial cancerHER2immunohistochemistryin-situ hybridisationinterobserver variability

Identifiers

PMID33835523
PMCPMC8518500
OpenAlexW3149083586

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.